Rituximab Hyaluronidase in Combination with Chemotherapy in Treating Aggressive B-cell Lymphoma in Uganda
- Histology and immunohistochemistry (CD20+) confirmed Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), or histology confirmed KSHV-associated multicentric Castleman disease with elevated blood KSHV viral load
- Cohort 1: Age should be equal to or greater than 15
- Cohort 2: Age: 2-15
- Measurable disease
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Able to provide informed consent (adults) or assent (children < 18 years) in English or Luganda
- Human immunodeficiency virus (HIV)-infected patients eligible if meet the following criteria: * CD4+ T-cell count > 200 cells/uL * HIV treatable with effective antiretroviral therapy that does not include agents with known significant drug-drug interactions with accompanying chemotherapy (ritonavir and cobicistat contraindicated)
- Previous therapy for lymphoma or KSHV-multicentric Castleman disease (MCD)
- History of hypersensitivity to rituximab
- Pregnant or nursing women. Men or women may not participate unless they have agreed to use effective contraception during treatment and for 12 months following completion of therapy
- Inadequate organ function, unless attributed to lymphoma or KSHV-MCD
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 times upper limit of normal
- Creatinine > 2 times upper limit than normal or calculated creatinine clearance < 60 mL/min
- New York Heart Association (NYHA) cardiac failure class III or IV
- Patients with clinically significant anemia-hemoglobin less than 10 g/dL
- Central nervous system (CNS) masses consistent with lymphoma or untreated infection; leptomeningeal disease will not be excluded
- Patients with malignancy within 5 years, other than resected local skin cancer or limited Kaposi sarcoma (KS) (no known pulmonary KS)
- Patients with evidence of active infections including malaria and hepatitis B (participants with hepatitis B virus [HBV] controlled on antivirals will not be excluded)
I. To evaluate the safety of subcutaneous rituximab and hyaluronidase human (rituximab hyaluronidase) in pediatric and adult participants with Burkitt lymphoma, diffuse large B-cell lymphoma, or Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease in Uganda when administered with standard chemotherapy and site-specific supportive care.
II. To evaluate weight-based dosing of subcutaneous rituximab hyaluronidase that minimizes extreme dose levels in pediatrics, defined as a Ctrough level below 25 ug/ml or above 400 ug/ml after the first subcutaneous dose.
I. To estimate response rates at the end of therapy.
II. To estimate overall survival, progression-free survival and disease-free survival at 1 year from initiation of therapy.
I. To evaluate the effect of age, weight, dose, dosing schedule and lactate dehydrogenase (LDH) on rituximab Ctrough in pediatrics and adults.
II. Evaluate gut microbiome at baseline, end of therapy, six months follow up visit and one year follow up visit, and explore associations of microbiome diversity and other characteristics with clinical parameters such as human immunodeficiency virus (HIV) infection status.
III. Evaluate KSHV and Epstein-Barr virus (EBV) viral load at baseline, end of therapy, six months follow up and one year follow up, and explore associations with clinical parameters.
IV. To compare response rate and survival to similar historical cohorts.
V. Explore the molecular characteristics of baseline tumors and their relationship to clinical parameters such as
complete response rate and overall survival.
VI. To bank blood, rectal swab and tissue specimens as well as data for future exploratory correlative studies.
OUTLINE: Open-label Phase I study characterizing the safety, tolerability, and activity of subcutaneous rituximab hyaluronidase (sqR) alone (KSHV-MCD), or combined with local standard of care chemotherapy (BL or DLBCL), in 2 age-based cohorts of patients:
1) Cohort 1: Age >= 15
2) Cohort 2: Age: 2-14
sqR dose for Cohort 1 (adults) will be 1400 mg (flat dose); sqR dose for Cohort 2 (pediatrics) will depend on patient weight: >= 35 kg: 1400 mg, < 35 kg: 700 mg. For all participants, sqR will be administered with local standard of care chemotherapy (BL, DLBCL) or alone (KSHV-MCD), and supportive care.
Each cohort comprises two Therapy Groups. Therapy Group 1: up to 6 participants and will receive the first cycle of rituximab IV, and subsequent cycles as flat-dose sqR. Therapy Group 2: up to 12 participants and will receive flat-dose sqR for all cycles.
Disease-specific chemotherapy to be administered with rituximab hyaluronidase include:
PEDIATRIC BURKITT LYMPHOMA (BL): cyclophosphamide, vincristine and prednisone followed by 6 cycles of cyclophosphamide, vincristine, and methotrexate (COP-COM).
DLBCL: 6 cycles of cyclophosphamide, doxorubicin, vincristine and prednisone PO on days 1-5 of cycle 1 (CHOP).
ADULT BL: 6 cycles modified dose: etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone PO on days 1-5 (adjusted EPOCH).
KSHV-MCD: Rituximab or rituximab hyaluronidase SC on days 1, 8, 15, and 22.
After completion of study treatment, patients are followed up at 30 days, 3, 6, 9 and 12 months.
Trial Phase Phase I
Trial Type Treatment
Fred Hutch / University of Washington Cancer Consortium
Thomas S. Uldrick
- Primary ID RG1001799
- Secondary IDs NCI-2019-01493, U028, 10040
- Clinicaltrials.gov ID NCT03864419